The Global HIV Vaccine Enterprise (the Enterprise) is a unique alliance of independent organizations around the world dedicated to accelerating the development of a preventive HIV vaccine. The Enterprise model represents a new global way of thinking about scientific problems and approaches to resolving them through the formulation of a shared Scientific Strategic Plan. The plan is based on the identification of gaps and opportunities, the use of common tools, optimized resources, and iterative learning. Most importantly, it represents a new way for scientists to engage as a global community of problem-solvers, sharing materials and information, and balancing collaboration with healthy competition. The Enterprise is a unique alliance of organizations that has the convening power to bring together an inclusive global alliance of top researchers, funders, advocacy groups, and stakeholders to catalyze fresh thinking, set new directions and advance global cooperation to develop an HIV vaccine.